Modern wound closure techniques are increasingly based on the use of so-called “tissue” adhesives. These are usually simple to use. Other advantages result from decreased scar formation during wound healing, less marked hypertrophy and the elimination of postoperative treatments.
At present, various types of tissue adhesives are commercially available. The so-called “fibrin” adhesives mainly consist of plasma proteins, in particular, fibrinogen and thrombin. These adhesives intervene actively in the clotting cascade and as a rule have good hemostatic properties. However, fibrin adhesives are normally produced from human or animal sources. Hence, their preparation is usually time- and above all cost-intensive. A further disadvantage lies in an infection risk to the patients which cannot be entirely excluded.
On the other hand, partly synthetic adhesives, for example, gelatin-resorcinol-formaldehyde, do often have higher adhesive strength than the fibrin adhesives described above. However, as a rule they have poorer hemostatic properties compared to the natural tissue adhesives. In principle, infections can still be transferred via the natural component of a partly synthetic adhesive. In addition, partly synthetic adhesives are often crosslinked with a toxic compound, for example, formaldehyde or glutaraldehyde.
In the meantime, exclusively synthetically produced tissue adhesives have also increasingly come into use. These adhesives are mainly compositions based on cyanoacrylates. At present, various cyanoacrylates are used as surgical adhesives. For example, the adhesive Dermabond® consists of n-octyl 2-cyanoacrylate. A further example is the adhesive product Histoacryl®, which contains n-butyl 2-cyanoacrylate. Tissue adhesives based on cyanoacrylates are usually rapid-curing. The use of cyanoacrylate adhesives does indeed give satisfactory results for surface wound care. However, there are certain concerns from the toxicological point of view concerning the use of cyanoacrylate adhesives for the treatment of internal wounds. A further point is that cyanoacrylate compounds react with biological tissues in a strongly exothermic reaction, owing to which healthy cells in the wound area can suffer lasting damage.
Since partly and also wholly synthetic tissue adhesives are subject to certain limitations in their medical applications, there is a constant search for alternative adhesive compositions. One alternative adhesive composition is, for example, described in EP 1 719 530 A2. However, the compositions disclosed there are slow-curing, owing to which their medical usability is also limited.
A surgical adhesive based on a urethane prepolymer and an unsaturated cyano compound is found in U.S. Pat. No. 4,740,534. The cyano compound can be a cyanoacrylate or a cyanoacrylonitrile. As already mentioned, the use of cyanoacrylate compounds in particular is subject to certain disadvantages.
A further biological adhesive is known from WO 2005/118011 A1. The adhesive composition described there contains a mixture of crosslinkable prepolymers which are modified with isocyanate groups. With this type of adhesive composition, a disadvantage is their comparatively low viscosity, as a result of which, particularly with heavily bleeding wounds, there is the danger of the composition being flushed out of the wound area. This adhesive composition also has a comparatively long gelling or curing time. This can lead to additional complications, particularly with severe hemorrhages.
It could therefore be helpful to provide a combination suitable, in particular, as an adhesive composition for adhesive bonding of biological tissues, which is simple to use and, in particular, is suitable both for internal and also for surface wound treatment.